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      Induction of Labor at Term with Oral Misoprostol or as a Vaginal Insert and Dinoprostone Vaginal Insert – A Multicenter Prospective Cohort Study Translated title: Geburtseinleitung am Termin mit Misoprostol oral oder als Vaginalinsert und Dinoproston Vaginalinsert – eine multizentrische prospektive Kohortenstudie

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          Abstract

          Introduction The efficacy, safety, and perinatal outcome of oral misoprostol (OM), a misoprostol vaginal insert (MVI), and a dinoprostone vaginal insert (DVI) for induction of labor at term was examined in a prospective multicenter cohort study (ethics committee vote 4154–07/14). The primary aims of the study were the induction-birth interval (IBI), the cumulative delivery rates after 12 h, 24 h, and 48 h as well as the mode of delivery.

          Method 322 pregnant women were included in four German tertiary perinatal centers (MVI 110, DVI 64, OM 148). They did not vary in age or BMI. Statistical analysis was carried out using a multivariate linear regression analysis and binary logistic regression analysis.

          Results With regards to the median IBI, MVI and OM were equally effective and superior to the DVI (MVI 823 min [202, 5587]; DVI 1226 min [209, 4909]; OM 847 min [105, 5201]; p = 0.006). Within 24 hours, 64% were able to deliver with DVI, 85.5% with MVI and 87.5% with OM (p < 0.01). The rates of secondary Caesarean sections (MVI 24.5%; DVI 26.6%; OM 18.9%) did not differ significantly. Uterine tachysystole was found in 20% with MVI, 4.7% with DVI and 1.4% with OM (p < 0.001). A uterine rupture did not occur in any of the cases. Perinatal acidosis occurred (umbilical cord arterial pH < 7.10) in 8.3% with MVI, 4.7 with DVI and 1% with OM (p = 0.32). Neonatal condition was only impaired in three cases (5-minute Apgar score < 5).

          Summary Induction of labor at term using the prostaglandins misoprostol and dinoprostone is an effective intervention that is safe for the mother and child. Oral application of misoprostol demonstrated the highest efficacy while maintaining a favorable safety profile.

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          Induction of labour for improving birth outcomes for women at or beyond term

          Beyond term, the risks of stillbirth or neonatal death increase. It is unclear whether a policy of labour induction can reduce these risks. This Cochrane review is an update of a review that was originally published in 2006 and subsequently updated in 2012 To assess the effects of a policy of labour induction at or beyond term compared with a policy of awaiting spontaneous labour or until an indication for birth induction of labour is identified) on pregnancy outcomes for infant and mother. We searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform ( ICTRP ) (9 October 2017), and reference lists of retrieved studies. Randomised controlled trials (RCTs) conducted in pregnant women at or beyond term, comparing a policy of labour induction with a policy of awaiting spontaneous onset of labour (expectant management). We also included trials published in abstract form only. Cluster‐RCTs, quasi‐RCTs and trials using a cross‐over design are not eligible for inclusion in this review. We included pregnant women at or beyond term. Since a risk factor at this stage of pregnancy would normally require an intervention, only trials including women at low risk for complications were eligible. We accepted the trialists' definition of 'low risk'. The trials of induction of labour in women with prelabour rupture of membranes at or beyond term were not considered in this review but are considered in a separate Cochrane review. Two reviewers independently assessed trials for inclusion, assessed risk of bias and extracted data. Data were checked for accuracy. We assessed the quality of evidence using the GRADE approach. In this updated review, we included 30 RCTs (reporting on 12,479 women). The trials took place in Norway, China, Thailand, the USA, Austria, Turkey, Canada, UK, India, Tunisia, Finland, Spain, Sweden and the Netherlands. They were generally at a moderate risk of bias. Compared with a policy of expectant management, a policy of labour induction was associated with fewer (all‐cause) perinatal deaths (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.14 to 0.78; 20 trials, 9960 infants; moderate‐quality evidence). There were two perinatal deaths in the labour induction policy group compared with 16 perinatal deaths in the expectant management group. The number needed to treat to for an additional beneficial outcome (NNTB) with induction of labour in order to prevent one perinatal death was 426 (95% CI 338 to 1337). There were fewer stillbirths in the induction group (RR 0.33, 95% CI 0.11 to 0.96; 20 trials, 9960 infants; moderate‐quality evidence); there was one stillbirth in the induction policy arm and 10 in the expectant management group. For women in the policy of induction arms of trials, there were fewer caesarean sections compared with expectant management (RR 0.92, 95% CI 0.85 to 0.99; 27 trials, 11,738 women; moderate‐quality evidence); and a corresponding marginal increase in operative vaginal births with induction (RR 1.07, 95% CI 0.99 to 1.16; 18 trials, 9281 women; moderate‐quality evidence). There was no evidence of a difference between groups for perineal trauma (RR 1.09, 95% CI 0.65 to 1.83; 4 trials; 3028 women; low‐quality evidence), postpartum haemorrhage (RR 1.09 95% CI 0.92 to 1.30, 5 trials; 3315 women; low‐quality evidence), or length of maternal hospital stay (average mean difference (MD) ‐0.34 days, 95% CI ‐1.00 to 0.33; 5 trials; 1146 women; Tau² = 0.49; I² 95%; very low‐quality evidence). Rates of neonatal intensive care unit (NICU) admission were lower (RR 0.88, 95% CI 0.77 to 1.01; 13 trials, 8531 infants; moderate‐quality evidence) and fewer babies had Apgar scores less than seven at five minutes in the induction groups compared with expectant management (RR 0.70, 95% CI 0.50 to 0.98; 16 trials, 9047 infants; moderate‐quality evidence). There was no evidence of a difference for neonatal trauma (RR 1.18, 95% CI 0.68 to 2.05; 3 trials, 4255 infants; low‐quality evidence), for induction compared with expectant management. Neonatal encephalopathy, neurodevelopment at childhood follow‐up, breastfeeding at discharge and postnatal depression were not reported by any trials. In subgroup analyses, no clear differences between timing of induction ( 287 days) gestation for the intervention arm. A policy of labour induction at or beyond term compared with expectant management is associated with fewer perinatal deaths and fewer caesarean sections; but more operative vaginal births. NICU admissions were lower and fewer babies had low Apgar scores with induction. No important differences were seen for most of the other maternal and infant outcomes. Most of the important outcomes assessed using GRADE had a rating of moderate or low‐quality evidence ‐ with downgrading decisions generally due to study limitations such as lack of blinding (a condition inherent in comparisons between a policy of acting and of waiting), or imprecise effect estimates. One outcome (length of maternal stay) was downgraded further to very low‐quality evidence due to inconsistency. Although the absolute risk of perinatal death is small, it may be helpful to offer women appropriate counselling to help choose between scheduled induction for a post‐term pregnancy or monitoring without (or later) induction). The optimal timing of offering induction of labour to women at or beyond term warrants further investigation, as does further exploration of risk profiles of women and their values and preferences. Individual participant meta‐analysis is likely to help elucidate the role of factors, such as parity, in influencing outcomes of induction compared with expectant management. Induction of labour in women with normal pregnancies at or beyond term What is the issue? A normal pregnancy lasts about 40 weeks from the start of the woman's last menstrual period, but anything from 37 to 42 weeks is considered as being at term (within the normal range). If a pregnancy goes too long, a woman and her clinician may wish to intervene to bring the birth on, for example, by induction. Why is this important? Births after 42 weeks' gestation may slightly increase risks for babies, including a greater risk of death (before or shortly after birth). However induction of labour may also have risks for mothers and their babies, especially if women are not ready to labour. No tests can predict if babies would be better to stay inside their mother or if labour should be induced to make the birth happen sooner. Many hospitals therefore have policies for how long pregnancies should continue. This update (originally published in 2006 and subsequently updated in 2012) looks to see if inducing labour at a set time at or beyond term, could reduce risks for the babies. What evidence did we find? We searched for evidence up 9 October 2017 and identified 30 trials with over 12,000 women. The trials took place in Norway, China, Thailand, the USA, Austria, Turkey, Canada, UK, India, Tunisia, Finland, Spain, Sweden and the Netherlands. The evidence was mostly of moderate quality. The trials compared a policy to induce labour at or later than term (usually after 41 completed weeks of gestation (> 287 days)) with waiting for labour to start and/or waiting for a period before inducing labour. We found that there were fewer deaths of babies in hospitals with a policy to induce when a pregnancy was continuing beyond term (moderate‐quality evidence). Fewer caesarean births were required with induction compared with waiting, but more assisted vaginal births were required with induction. There were fewer admissions to the intensive care nursery and fewer low Apgar scores at five minutes after birth (a simple test to test babies' health) in the induction groups compared with waiting (moderate‐quality evidence). We found that there were no clear differences between a policy to induce at or later than term or waiting in the risks of mothers having trauma to their perineum or bleeding after birth (both low‐quality evidence), in the length of their hospital stay (very‐low quality evidence), or in their babies having trauma (low‐quality evidence), None of the trials provided information on breastfeeding at discharge from hospital, postnatal depression, or whether the babies had encephalopathy (early abnormal neurological function), or child development. What does this mean? A policy of labour induction compared with expectant management is associated with fewer deaths of babies and fewer caesarean sections; but more assisted vaginal births. Although the chances of babies dying are small, it may help to offer women appropriate counselling to make an informed choice between induction of labour for pregnancies at, or later than, term ‐ or waiting for labour to start and/or waiting before inducing labour. The best time to offer induction of labour to women at or beyond term is not yet clear and warrants further investigation. The risk profiles of women as well as their values and preferences could also be considered.
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            WHO recommendations for misoprostol use for obstetric and gynecologic indications.

            Misoprostol, a prostaglandin E1 analog, stimulates uterine contractility and cervical ripening. A number of randomized trials and systematic reviews have evaluated its use in obstetric and gynecologic conditions. Misoprostol is inexpensive, stable at room temperature, and available in more than 80 countries, making it particularly useful in resource-poor settings. WHO recognizes the crucial role of misoprostol in reproductive health and has incorporated recommendations for its use into 4 reproductive health guidelines focused on induction of labor, prevention and treatment of postpartum hemorrhage, and management of spontaneous and induced abortion.
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              Labour induction with prostaglandins: a systematic review and network meta-analysis

              Objectives To assess the effectiveness and safety of prostaglandins used for labour induction. Design Systematic review with Bayesian network meta-analysis Data sources The Cochrane Pregnancy and Childbirth Group’s Database of Trials (which incorporates the results of a broad generic search for all pregnancy and postpartum trials). Sources included are CENTRAL, Medline, Embase, NHS Economic Evaluation Database, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials. Eligibility criteria for selecting studies Randomised clinical trials of prostaglandin or prostaglandin analogues used for third trimester cervical ripening or labour induction versus placebo or no treatment, alternative prostaglandin dose or administration, or a different type of prostaglandin. We included studies recruiting women with a viable fetus, but had no other restrictions relating to indication for labour induction or language of publication. Outcomes assessed were serious neonatal morbidity (trialist defined) or perinatal death; serious maternal morbidity (trialist defined) or death; vaginal delivery not achieved within 24 hours, caesarean section, and uterine hyperstimulation with fetal heart rate changes. Results 280 randomised clinical trials were included (48 068 women) in the review. Maternal and neonatal mortality and serious morbidity were rarely reported and are summarized narratively. Unresolved inconsistency was observed for the hyperstimulation outcome. Relative to placebo, the odds of failing to achieve a vaginal delivery were lowest for vaginal misoprostol (≥50 µg) (odds ratio 0.06 (95% credible interval 0.02 to 0.12)), with a 39% absolute probability of event (95% credible interval 1% to 94%). Compared with placebo, odds of caesarean section were lowest for titrated oral misoprostol solution (<50 µg) (odds ratio 0.65 (0.49 to 0.83)), with an absolute probability of event of 15% (3% to 40%). Conclusions Low dose(<50 µg) titrated oral misoprostol solution had the lowest probability of caesarean section, whereas vaginal misprostol (≥50 µg) had the highest probability of achieving a vaginal delivery within 24 hours. These findings have important implications for a series of current national and international guidelines for induction of labour and future research in this area. Systematic review registration PROSPERO 2013:CRD42013005116
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                Author and article information

                Journal
                Geburtshilfe Frauenheilkd
                Geburtshilfe Frauenheilkd
                10.1055/s-00000020
                Geburtshilfe und Frauenheilkunde
                Georg Thieme Verlag KG (Rüdigerstraße 14, 70469 Stuttgart, Germany )
                0016-5751
                1438-8804
                10 August 2022
                August 2022
                1 August 2022
                : 82
                : 8
                : 868-873
                Affiliations
                [1 ]Ringgold 39065, Klinik für Geburtsmedizin, Universitätsklinikum Jena, Jena, Germany;
                [2 ]Klinik für Geburtshilfe, Krankenhaus St. Elisabeth und St. Barbara Halle, Halle, Germany
                [3 ]Frauenklinik, St. Joseph Krankenhaus Berlin-Tempelhof GmbH, Berlin, Germany
                [4 ]Ringgold 27157, Klinik für Geburtsmedizin, Vivantes Klinikum Neukölln, Berlin, Germany;
                Author notes
                Korrespondenzadresse Prof. Ekkehard Schleußner Ringgold 39065, Universitätsklinikum Jena, Klinik für Geburtsmedizin; Am Klinikum 107747 JenaGermany Ekkehard.Schleussner@ 123456med.uni-jena.de
                Author information
                http://orcid.org/0000-0002-2903-391X
                Article
                10.1055/a-1860-0419
                9365496
                35967743
                1ff979d5-469f-4c03-85f7-b666061bb809
                The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited.

                History
                : 17 January 2021
                : 20 May 2022
                Categories
                GebFra Science
                Original Article

                induction of labor,prostaglandins,misoprostol,dinoprostone

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